Lysyl oxidases (LOX, LOXL, LOXL2, etc.; amine oxidase family) are Cu-dependent enzymes that oxidize lysine into allysine (α-aminoadipic-δ-semialdehyde) [Kagan H M. et al., J. Cell. Biochem. 2003; 88:660]. LOX have been implicated in crosslink formation in stromal collagens and elastins. LOX are elevated in hypoxic tumors and affect cell motility, tumor development and progression of metastasis [Kirschmann D A. et al., Cancer Res. 2002; 62:4478]. This elevation is mechanistically important for breast cancer metastasis and invasion as well as in other cancers including colon and esophagus [Fong S F, et al. genes Chromosomes Cancer 2007; 6:644], and is based on the formation of Schiff-base linkages (aldehyde+amine) or aldol condensation products (aldehyde+aldehyde), allowing cancer cells to latch on to other cells/tissues. There are other mechanisms of LOX involvement into metastasis progression—for example, the recruitment of bone marrow—derived cells [Erler J T et al. Nature 2006; 440:1222-1226; Erler J T. et al., Cancer Res. 2006; 66:10238; Erler I T et al. Cancer Cell 2009; 15:35-44 ] for a so-called premetastatic niche formation.
LOX oxidises Lys of collagens, elastins and other proteins to allysine and/or

5-hydroxylysine. These can then form cross-links, for example as shown below:

A reaction important in metastatic development. It is therefore desirable to reduce the activity of lysyl oxidase in cancer. As with any cancer treatment, it is also desirable that this does not completely block the enzyme activity, so as to minimize the adverse effects of therapy on other aspects of physiology.
It is therefore desirable to reduce the activity of extracellular LOX in cancer. Some current approaches involve LOX inhibitors (e.g. β-aminopropionitrile [Jackson L E. et al., Biochem. Biophys. Res. Commun. 1991; 179:939]), sequestration of Cu, and the use of antibodies [Erler J T et al., Nature 2006; 440:1222]. As with any cancer treatment, it is also desirable that this does not completely block the enzyme activity, so as to minimize the adverse effects of therapy on other aspects of physiology. For example, inhibition of LOX is known to cause increased elasticity of blood vessels etc., leading to aneurisms. Besides, these methods are likely to be immunogenic, as well as bringing further complications such as toxicity.
It is known that the rate of some reactions breaking or forming chemical bonds is affected by the nature of the isotopes of the atoms, which the bond links. In general, bonds terminating in a heavy isotope will be less liable to cleavage than a bond terminating in a lighter isotope. Of particular note is that bonds between hydrogen atoms and other atoms are less liable to breakage if the hydrogen is 2H rather than 1H. A similar effect is seen when comparing the rate of cleavage of a bond between a carbon atom and another atom, where bonds with 13C are less liable to cleavage than bonds with 12C. This is known as the Kinetic Isotope Effect, and is well described. Many isotopes are known to show this effect, as is described in Isotope effects in chemical reactions. (C. J. Collins, N. S. Bowman (eds.) 1970). It is known that these effects are also manifest in enzyme-catalyzed reactions, as described in. Isotope effects on enzyme-catalyzed reactions (Cleland, W. W., M. H. O'Leary, and D. B. Northrop (eds.) 1976).